Project Abstract A significant public health development, pre-exposure prophylaxis (PrEP) is now being widely promoted as a prevention strategy for individuals in high-risk groups, such as men who have sex with men who report substance-use (past 6-month illegal drug use and/or heavy alcohol use). While this is an exciting development, rapid identification of these high-risk patients and the ability to provide brief consultation and prescription or referral for PrEP services by primary care staff remains a major concern. The proposed mixed methods study aims to develop and pilot-test a PrEP screening instrument for facilitating PrEP uptake among substance-using MSM that will be integrated into clinic workflow based on provider-identified barriers and facilitators to sexual-health screening. The study will take place in a single primary care clinic contained within a larger integrated healthcare delivery system, Kaiser Permanente Southern California (KPSC). Identification of both the provider- and patient-level barriers to PrEP uptake among high-risk substance-using MSM within a large integrated healthcare system will inform future intervention efforts aimed at mitigating HIV health disparities. The proposed 2-year pilot study will involve the collection of preliminary data to inform the development of a larger formal evaluation study. This project is significant in that it seeks to develop and test a screening instrument that will be administered to patients during appointment check-in and made available to their primary care provider for the rapid identification of substance-using MSM at high-risk for HIV acquisition in order to facilitate PrEP prescription/referral. This project is innovative in its focus on the identification of potential provider-, patient-, and system-level barriers to PrEP uptake among these patients.